Influence of High Hemoglobin-Oxygen Affinity on Humans During Hypoxia

Humans elicit a robust series of physiological responses to maintain adequate oxygen delivery during hypoxia, including a transient reduction in hemoglobin-oxygen (Hb-O2) affinity. However, high Hb-O2 affinity has been identified as a beneficial adaptation in several species that have been exposed to high altitude for generations. The observed differences in Hb-O2 affinity between humans and species adapted to high altitude pose a central question: is higher or lower Hb-O2 affinity in humans more advantageous when O2 availability is limited? Humans with genetic mutations in hemoglobin structure resulting in high Hb-O2 affinity have shown attenuated cardiorespiratory adjustments during hypoxia both at rest and during exercise, providing unique insight into this central question. Therefore, the purpose of this review is to examine the influence of high Hb-O2 affinity during hypoxia through comparison of cardiovascular and respiratory adjustments elicited by humans with high Hb-O2 affinity compared to those with normal Hb-O2 affinity.

Acid-base balance at high altitude in lowlanders and indigenous highlanders

High-altitude exposure results in a hyperventilatory-induced respiratory alkalosis followed by renal compensation (bicarbonaturia) to return arterial blood pH(a) toward sea-level values. However, acid-base balance has not been comprehensively examined in both lowlanders and indigenous populations - where the latter are thought to be fully adapted to high-altitude. The purpose of this investigation was to compare acid-base balance between acclimatizing lowlanders, and Andean and Sherpa highlanders at various altitudes (~3,800, ~4,300, and ~5,000 m). We compiled data collected across five independent high-altitude expeditions and report the following novel findings: 1) at 3,800 m, Andeans (n=7) had elevated pHa compared to Sherpas (n=12; P<0.01), but not to lowlanders (n=16; nine days acclimatized; P=0.09); 2) at 4,300 m, lowlanders (n=16; 21 days acclimatized) had elevated pHa compared to Andeans (n=32) and Sherpas (n=11; both P<0.01), and Andeans had elevated pHa compared to Sherpas (P=0.01); and 3) at 5,000 m, lowlanders (n=16; 14 days acclimatized) had higher pHa compared to both Andeans (n=66) and Sherpas (n=18; P<0.01, and P=0.03, respectively), and Andean and Sherpa highlanders had similar blood pHa (P=0.65). These novel data characterize acid-base balance acclimatization and adaptation to various altitudes in lowlanders and indigenous highlanders.

Rescue Emergencies Due to High-Altitude Illnesses Are Rare in Switzerland

Background: Despite a potential high risk of acute mountain sickness (AMS) in the Swiss Alps, there is a lack of analyses concerning its relevance over longer periods. In consequence, the aim of this study is to analyze the prevalence of AMS in comparison to other causes of mountain emergencies in recent years in Switzerland. Material and Methods: Based on the central registry of mountain emergencies of the Swiss Alpine Club (SAC), all cases in the period between 2009 and 2020 were analyzed for AMS including the most severe forms of high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE). Emergencies were assessed for the severity of the event with a National Advisory Committee for Aeronautics (NACA) score. Results: From a total of 4596 high-altitude mountaineering emergencies identified in the observational period, a total number of 352 cases of illnesses were detected. Detailed analysis revealed 85 cases of AMS, 5 cases of HAPE, and 1 case of HACE. The average altitude was 3845 ± 540 m. Most cases were in the canton of Valais, especially in the Monte Rosa region and the mountains of the Mischabel group (Täschhorn, Dom, Südlenz, Nadelhorn, Hohberghorn). There were only three deaths related to high-altitude illnesses; all the other events could be identified as moderate to severe but not life-threatening. Discussion: An emergency due to AMS that requires rescue is unlikely in the Swiss Alps. This does not imply that AMS is not a concern. However, the facts that the maximal altitude is relatively low and that fast self-descents often seem possible probably minimize the likelihood that mountaineers with symptoms contact emergency services.

Right Ventricular Response to Acute Hypoxia Exposure: A Systematic Review

Background: Acute hypoxia exposure is associated with an elevation of pulmonary artery pressure (PAP), resulting in an increased hemodynamic load on the right ventricle (RV). In addition, hypoxia may exert direct effects on the RV. However, the RV responses to such challenges are not fully characterized. The aim of this systematic review was to describe the effects of acute hypoxia on the RV in healthy lowland adults.Methods: We systematically reviewed PubMed and Web of Science and article references from 2005 until May 2021 for prospective studies evaluating echocardiographic RV function and morphology in healthy lowland adults at sea level and upon exposure to simulated altitude or high-altitude.Results: We included 37 studies in this systematic review, 12 of which used simulated altitude and 25 were conducted in high-altitude field conditions. Eligible studies reported at least one of the RV variables, which were all based on transthoracic echocardiography assessing RV systolic and diastolic function and RV morphology. The design of these studies significantly differed in terms of mode of ascent to high-altitude, altitude level, duration of high-altitude stay, and timing of measurements. In the majority of the studies, echocardiographic examinations were performed within the first 10 days of high-altitude induction. Studies also differed widely by selectively reporting only a part of multiple RV parameters. Despite consistent increase in PAP documented in all studies, reports on the changes of RV function and morphology greatly differed between studies.Conclusion: This systematic review revealed that the study reports on the effects of acute hypoxia on the RV are controversial and inconclusive. This may be the result of significantly different study designs, non-compliance with international guidelines on RV function assessment and limited statistical power due to small sample sizes. Moreover, the potential impact of other factors such as gender, age, ethnicity, physical activity, mode of ascent and environmental factors such as temperature and humidity on RV responses to hypoxia remained unexplored. Thus, this comprehensive overview will promote reproducible research with improved study designs and methods for the future large-scale prospective studies, which eventually may provide important insights into the RV response to acute hypoxia exposure.

Analysis of Inducing Factors of Chronic Pulmonary Heart Disease Caused by Chronic Obstructive Pulmonary Disease at High Altitude through Epidemiological Investigation under Intelligent Medicine and Big Data

This study explores the risk factors of chronic pulmonary heart disease (CPHD) induced by plateau chronic obstructive pulmonary disease (COPD) based on intelligent medical treatment and big data of electrocardiogram (ECG) signal. Based on GPU, a wavelet algorithm is introduced to extract features of ECG signal, and it was combined with generalized regression neural network (GRNN) to improve classification accuracy. From June 2018 to December 2020, 10,185 patients diagnosed with COPD in the plateau area by pulmonary function testing, ECG, and chest X-ray at X Hospital are taken as the research objects to evaluate the distribution of CPHD incidence at different ages and altitudes. The running time of GTX780Ti is about 15 times shorter than that of CPU. The accuracy of N detection based on the GPU-accelerated neural network model reached 98.06%. Accuracy (Acc), sensitivity (Se), specificity (Sp), and positive rate (PR) of V were 99.03%, 89.17%, 98.92%, and 93.18%, respectively. The Acc, Se, Sp, and PR of S were 99.54%, 86.22%, 99.74%, and 92.56%, respectively. The GRNN classification accuracy was up to 98%. 19% of COPD patients were diagnosed with CPHD, including 1,409 males (72.82%) and 526 females (36.24%). The highest prevalence of CPHD was 64.60% when the altitude was 1,900–2,499 m, and the prevalence was only 2.43% when the altitude was ≥3,500 m. The highest prevalence of CPHD was 63.77% at the age of 61–70 years, and the lowest prevalence at the age of 15∼20 years was only 0.26%. Therefore, the GPU-based neural network model improved the classification accuracy of ECG signals. Age and altitude were risk factors for CPHD induced by high-altitude COPD, which provided a reference for the prevention, diagnosis, and treatment of CPHD in high-altitude areas.

The Extension of Vegetable Production to High Altitudes Increases the Environmental Cost and Decreases Economic Benefits in Subtropical Regions

Global warming has driven the expansion of cultivated land to high-altitude areas. Intensive vegetable production, which is generally considered to be a high economic value and high environmental risk system, has expanded greatly in high-altitude mountainous areas of China. However, the environmental cost of vegetable production in these areas is poorly understood. In this study, we investigated pepper production at low (traditional pepper production area) and high (newly expanded area) altitudes in Shizhu, a typical pepper crop area. The output and environmental cost at the two altitudes were identified. We evaluated the influence of resource inputs, climate, and soil properties on pepper production. There were obvious differences in output and environmental cost between the two altitudes. High-altitude pepper production achieved a 16.2% lower yield, and had a higher fertilizer input, resulting in a 22.3% lower net ecosystem economic benefit (NEEB), 23.0% higher nitrogen (N) footprint and 24.0% higher carbon (C) footprint compared to low-altitude farming. There is potential for environmental mitigation with both high- and low-altitude pepper production; Compared to average farmers, high yield farmers groups reduced their N and C footprints by 16.9–24.8% and 18.3–25.2%, respectively, with 30.6–34.1% higher yield. A large increase in yield could also be achieved by increasing the top-dress fertilizer rate and decreasing the plant density. Importantly, high-altitude pepper production was achieved despite less advanced technology and inferior conditions (e.g., a poor road system and uneven fields). It provides a reference for the study on environmental cost of other high-altitude regions or other crop systems at high altitude area.

The effect of oxygen supply and oxygen distribution on single-head tunnel with different altitudes under mixed ventilation

Hypoxia plays a major role in limiting the construction of the high-altitude mine. Understanding the effect and the distribution of diffused oxygen supply at different altitudes is the premise for the design of a mine with oxygen supply system and the full utilization of oxygen resources. For the optimal design of an oxygen supply mode and ventilation system, a multi-component fluid model of the diffused oxygen supply of a single-head tunnel was developed. This study reveals the variation law of the average oxygen mass fraction at different altitudes. The relationship between the distance from the heading face and the oxygen mass fraction at each altitude was fitted. The results show that the distribution of oxygen mass fraction in a single head tunnel at different altitudes presents a similar trend of increasing first and then decline. In addition, the change of the average oxygen mass fraction with the increase of altitude is not linear, and the dispersion loss is larger in high-altitude areas. The largest oxygen enrichment area is distributed at the altitudes of 4000–4500 m. This study provides theoretical support for improving the hypoxic environment of high-altitude metal mines excavation work.

Association of Elevated Non-HDL-C and LDL-C with Carotid atherosclerosis among Tibetans Living at High Altitudes: A Cross-sectional Study

Background: Hypoxic circumstances impair endothelial function and may contribute to carotid atherosclerosis. In high-altitude areas, there is a scarcity of data on the correlation between lipid particles and carotid atherosclerosis. Methods: A total of 587 patients who underwent carotid artery ultrasound and met the inclusion and exclusion criteria were enrolled in our cross-sectional study. All participants resided in Luhuo County, Ganzi Tibetan Autonomous Prefecture, Sichuan Province, China (mean altitude: 3,860 meters). We used questionnaires, physical examination, blood sample testing, and ultrasound in our investigation. Spearman correlation analysis and multiple linear regression analysis were performed to explore the association between lipid particles and carotid atherosclerosis. We compared the disparity between lipid particles in predicting atherosclerosis using the receiver operator characteristic curve.Results: We found a statistically significant association between lipid particles and carotid atherosclerosis. After adjustment for certain variables, including age, gender, mean arterial pressure, and fasting blood glucose, we discovered that non-high-density lipoprotein-cholesterol (non-HDL-C) was a risk factor for carotid intima-media thickness (β = 0.012, p = 0.032) but not for low-density lipoprotein cholesterol (LDL-C) (p = 0.073). In terms of lifestyle, non-HDL-C was also found to be a risk factor for atherosclerosis independent of cigarette smoking and vegetarian (β = 0.012, p = 0.049). The area under the curve (AUC) of non-HDL-C was 0.644 (CI: 0.583 – 0.706) while LDL-C was 0.599 (CI: 0.534 - 0.664) in predicting carotid atherosclerosis. The optimal cut-off value of non-HDL-C was 3.625 mmol/L in predicting carotid plaques. Conclusions: Among Tibetans living in high-altitude areas, non-HDL-C is a better biomarker than LDL-C for carotid artery atherosclerosis independent of conventional risk factors. It is crucial to resolve non-HDL-C dyslipidemia in order to mitigate carotid atherosclerosis in Tibetans living at high-altitude settings.